乳腺癌是一種異質(zhì)性疾病，特征不一的腫瘤細(xì)胞及其相關(guān)健康細(xì)胞共同構(gòu)成決定疾病進(jìn)展和治療效果的生態(tài)系統(tǒng)。不過，乳腺癌生態(tài)系統(tǒng)特征及其與臨床數(shù)據(jù)的相關(guān)性尚不明確。
2019年4月11日，全球自然科學(xué)三大旗艦期刊之一、美國(guó)《細(xì)胞》正刊在線發(fā)表瑞士蘇黎世大學(xué)、蘇黎世聯(lián)邦理工學(xué)院、IBM蘇黎世研究院、巴塞爾大學(xué)醫(yī)院、巴塞爾大學(xué)、蘇黎世大學(xué)醫(yī)院、德國(guó)慕尼黑患者腫瘤銀行生物樣本庫(kù)、約瑟夫病理學(xué)研究所、馬爾堡大學(xué)醫(yī)院的研究報(bào)告，通過質(zhì)量細(xì)胞計(jì)數(shù)法，分析了144例人類乳腺腫瘤和50例非腫瘤組織標(biāo)本。
該研究利用腫瘤和免疫細(xì)胞抗體組，評(píng)估了2600萬(wàn)個(gè)細(xì)胞的73種蛋白質(zhì)表達(dá)。腫瘤的細(xì)胞組成特征顯著，包括表現(xiàn)型異常和表現(xiàn)型優(yōu)勢(shì)。腫瘤與免疫細(xì)胞之間的相關(guān)性分析表明，某些生態(tài)系統(tǒng)特征與免疫抑制和不良預(yù)后相關(guān)。高分級(jí)雌激素受體陽(yáng)性和雌激素受體陰性腫瘤可見大量PD-L1陽(yáng)性腫瘤相關(guān)巨噬細(xì)胞以及被大量消耗的T淋巴細(xì)胞。
因此，乳腺癌表現(xiàn)出腫瘤細(xì)胞表現(xiàn)型異常和腫瘤個(gè)體化，腫瘤與免疫的腫瘤生態(tài)系統(tǒng)相關(guān)性對(duì)于不同患者而不同。該大樣本單細(xì)胞蛋白質(zhì)組學(xué)分析揭示了腫瘤生態(tài)系統(tǒng)的腫瘤與免疫細(xì)胞多樣性，加深了我們對(duì)乳腺腫瘤生態(tài)系統(tǒng)的了解，并且表明根據(jù)生態(tài)系統(tǒng)對(duì)患者進(jìn)行分類，將有助于確定針對(duì)腫瘤及其免疫環(huán)境的個(gè)體化精準(zhǔn)治療方法。
Cell. 2019 Apr 11. [Epub ahead of print]
A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer.
Johanna Wagner, Maria Anna Rapsomaniki, Stéphane Chevrier, Tobias Anzeneder, Claus Langwieder, August Dykgers, Martin Rees, Annette Ramaswamy, Simone Muenst, Savas Deniz Soysal, Andrea Jacobs, Jonas Windhager, Karina Silina, Maries van den Broek, Konstantin Johannes Dedes, Maria Rodríguez Martínez, Walter Paul Weber, Bernd Bodenmiller.
University of Zurich, Zurich, Switzerland; ETH Zurich, Zurich, Switzerland; IBM Research Zurich, Rueschlikon, Switzerland; Patients' Tumor Bank of Hope (PATH) Biobank, Munich, Germany; Institute of Pathology at Josefshaus, Dortmund, Germany; University Hospital Giessen and Marburg, Marburg, Germany; University Hospital Basel and University of Basel, Basel, Switzerland; University Hospital Zurich, Zurich, Switzerland.
HIGHLIGHTS
Single-cell proteomics reveals tumor and immune cell diversity in tumor ecosystems
Breast cancer exhibits tumor cell phenotypic abnormalities and tumor individuality
PD-L1+ TAMs and exhausted T cells are abundant in high-grade ER- and ER+ tumors
Tumor-immune relationships in the tumor ecosystem are patient-stratifying
Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry. The expression of 73 proteins in 26 million cells was evaluated using tumor and immune cell-centric antibody panels. Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. High frequencies of PD-L1+ tumor-associated macrophages and exhausted T cells were found in high-grade ER+ and ER- tumors. This large-scale, single-cell atlas deepens our understanding of breast tumor ecosystems and suggests that ecosystem-based patient classification will facilitate identification of individuals for precision medicine approaches targeting the tumor and its immunoenvironment.
KEYWORDS: breast cancer; tumor ecosystem; tumor heterogeneity; immunosuppression; T cell; macrophage; single-cell analysis; mass cytometry
DOI: 10.1016/j.cell.2019.03.005
聯(lián)系客服
